Phenylketonuria (PKU)

Description - This metabolic disorder is caused by a recessively inherited defect in which the body cannot use the amino acid phenylalanine properly. Phenylalanine, found in all dietary protein, accumulates in the blood due to the absence of the enzyme phenylalanine hydroxylase. This enzyme is responsible for catalyzing the conversion of phenylalanine to tyrosine.

Clinical Features - Without the enzyme in classical PKU, the serum phenylalanine level will quickly rise from a normal level of less than 2.1 mg/dl to greater than 20 mg/dl. Asymptomatic in the immediate newborn period, untreated PKU will present with the onset of developmental delay. After four to six weeks a musty odor may be noted in the urine. By a year of age, mental and motor retardation, microcephaly, decreased growth rate, seizures or tremors will be evident. Most untreated PKU patients (96-98%) will have an IQ of less than fifty.

Treatment - Treatment must begin as early as possible and should be continued indefinitely. However, treatment should not be started until the diagnosis has been confirmed by a specialist. Treatment consists of selectively restricting dietary phenylalanine except for the precise amount needed for growth and development. This is accomplished by use of a special formula in infancy and a diet low in phenylalanine but adequate in other nutrients. The infant’s growth and development are followed closely, in conjunction with dietary monitoring by a trained nutritionist and periodic determinations of blood levels of phenylalanine. Successful treatment can result in normal physical and mental development. Undue delay can cause harm to the infant.

Variant Forms of PKU - There are several intermediate forms of hyperphenylalaninemia in which the serum phenylalanine (phe) levels are lower than classical PKU. In these cases, mental retardation is variable and, in the milder variants, is completely absent. Blood levels may remain high throughout life or may gradually fall toward normal. In infancy, these patients can mimic the severe PKU condition, and even in mild cases there seems to be an increased risk of the maternal PKU syndrome.

Forms of hyperphenlalaninemia caused by defects of biopterin metabolism have been recognized. All infants with persistently abnormal levels of phenylalanine, however, slight should be tested by special blood and urine tests for biopterin abnormalities. It is very important that none of the infants referred to treatment centers be placed on any kind of protein restriction prior to medical workup.

Maternal PKU and Hyperphenylalaninemia - Women with any significant degree of hyperphenylalaninemia have an increased risk of miscarriage, and their offspring (who may not have PKU) may have intrauterine growth retardation, which lasts postnatally. More than 90 percent of these infants have microcephaly, mental retardation and congenital heart defects. They have a transient elevation of phenylalanine (4-20 mg/dl), which falls to normal within 24 hours. A medically supervised phenylalanine restricted diet begun before conception with phe levels maintained within a safe range throughout pregnancy may prevent damage to the fetus.